TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13861	41806;41807;41808	chr2:178635990;178635989;178635988	chr2:179500717;179500716;179500715
N2AB	12220	36883;36884;36885	chr2:178635990;178635989;178635988	chr2:179500717;179500716;179500715
N2A	11293	34102;34103;34104	chr2:178635990;178635989;178635988	chr2:179500717;179500716;179500715
N2B	4796	14611;14612;14613	chr2:178635990;178635989;178635988	chr2:179500717;179500716;179500715
Novex-1	4921	14986;14987;14988	chr2:178635990;178635989;178635988	chr2:179500717;179500716;179500715
Novex-2	4988	15187;15188;15189	chr2:178635990;178635989;178635988	chr2:179500717;179500716;179500715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-88
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.4985
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/A	rs1553746267	None	0.042	N	0.339	0.123	0.104622674875	gnomAD-4.0.0	3.20883E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.77317E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.2381	likely_benign	0.2347	benign	-0.632	Destabilizing	0.042	N	0.339	neutral	N	0.350138294	None	None	N
E/C	0.9241	likely_pathogenic	0.9243	pathogenic	-0.268	Destabilizing	0.958	D	0.445	neutral	None	None	None	None	N
E/D	0.5082	ambiguous	0.5209	ambiguous	-0.768	Destabilizing	None	N	0.097	neutral	N	0.351323942	None	None	N
E/F	0.9083	likely_pathogenic	0.9135	pathogenic	-0.18	Destabilizing	0.858	D	0.551	neutral	None	None	None	None	N
E/G	0.4786	ambiguous	0.4995	ambiguous	-0.93	Destabilizing	0.042	N	0.309	neutral	N	0.34595872	None	None	N
E/H	0.7184	likely_pathogenic	0.7108	pathogenic	-0.164	Destabilizing	0.495	N	0.441	neutral	None	None	None	None	N
E/I	0.563	ambiguous	0.5614	ambiguous	0.155	Stabilizing	0.665	D	0.593	neutral	None	None	None	None	N
E/K	0.3504	ambiguous	0.3648	ambiguous	-0.062	Destabilizing	None	N	0.071	neutral	N	0.345048885	None	None	N
E/L	0.7026	likely_pathogenic	0.7077	pathogenic	0.155	Stabilizing	0.218	N	0.527	neutral	None	None	None	None	N
E/M	0.6575	likely_pathogenic	0.6662	pathogenic	0.383	Stabilizing	0.665	D	0.447	neutral	None	None	None	None	N
E/N	0.626	likely_pathogenic	0.6245	pathogenic	-0.587	Destabilizing	0.218	N	0.381	neutral	None	None	None	None	N
E/P	0.9544	likely_pathogenic	0.9407	pathogenic	-0.086	Destabilizing	0.362	N	0.536	neutral	None	None	None	None	N
E/Q	0.1594	likely_benign	0.1523	benign	-0.485	Destabilizing	0.003	N	0.141	neutral	N	0.34409478	None	None	N
E/R	0.5118	ambiguous	0.515	ambiguous	0.238	Stabilizing	0.123	N	0.379	neutral	None	None	None	None	N
E/S	0.3163	likely_benign	0.3151	benign	-0.781	Destabilizing	0.002	N	0.093	neutral	None	None	None	None	N
E/T	0.3027	likely_benign	0.3038	benign	-0.53	Destabilizing	0.123	N	0.423	neutral	None	None	None	None	N
E/V	0.3255	likely_benign	0.3337	benign	-0.086	Destabilizing	0.174	N	0.441	neutral	N	0.343267797	None	None	N
E/W	0.978	likely_pathogenic	0.9798	pathogenic	0.08	Stabilizing	0.958	D	0.477	neutral	None	None	None	None	N
E/Y	0.8754	likely_pathogenic	0.8883	pathogenic	0.088	Stabilizing	0.665	D	0.571	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.